Epinephrine promotes IL-8 production in human leukocytes via an effect on platelets

Interleukin-8 (IL-8) is generally accepted to be an important mediator of a number of acute and chronic inflammatory diseases and is produced by monoc ytes upon stimulation by lipopolysaccharide (LPS). Epinephrine has been rep orted by several groups to suppress activation of monocytes in response to LPS, and the aim of the present study was to examine the effect of epinephr ine on LPS induced IL-8 production using whole blood as a model system. Epi nephrine increased LPS induced IL-8 production in a dose-dependent manner i n the whole concentration range (0.001-100 mu M) and 1 mu M epinephrine inc reased IL-8 levels with 125%. Epinephrine per se had no effect on IL-8 leve ls. The potentiating effect of epinephrine was mediated by blood platelets, since IL-8 levels in samples containing platelets and stimulated with LPS and epinephrine (1-100 mu M) were significantly higher (p < 0.05) than in c ontrol samples containing no platelets. This effect of platelets seemed to be due to platelet release products, since addition of 25 mu l platelet lys ate supernatant to whole blood increased LPS induced IL-8 production with 1 00% and a similar effect was observed in freshly isolated mononuclear cells resuspended in plasma. Upon addition of 50 mu g/ml of the carboxyterminal peptide of platelet factor 4 (PF4(58-70)) to whole blood, LPS stimulated IL -8 levels were increased with 115%, whereas in mononuclear cells, 20 mu g/m l PF4(58-70) enhanced IL-8 production with 40%. We demonstrate for the firs t time that epinephrine promotes LPS induced production of IL-8 in whole bl ood via an effect on blood platelets. This potentiating effect of platelets is shown to be due to platelet granule contents, and platelet factor 4 (PF 4) is suggested to be one of several platelet granule proteins promoting LP S induced IL-8 production in whole blood.